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Rheumatology
Vasculitis: ANCA-associated (GPA, MPA, EGPA)
ANCA-associated vasculitides (AAV) are necrotizing small-vessel vasculitides with few or no immune deposits ("pauci-immune"). Three entities:
Suspect AAV when:
Board pearl: AAV is the most common cause of pulmonary-renal syndrome; always order ANCA when AKI + hemoptysis coexist.
GPA (formerly Wegener's) — classic triad: upper airway, lower airway, kidneys
Upper airway (>90%):
Lower airway:
Renal:
Other:
Key distinction: Cavitary lung lesions + upper airway destruction strongly favors GPA over MPA.
MPA:
EGPA (formerly Churg-Strauss):
Board pearl: Eosinophilic myocarditis/cardiomyopathy is the #1 cause of death in EGPA — always evaluate cardiac function early.
ANCA testing:
Other labs:
Key distinction: ANCA specificity (PR3 vs MPO by immunoassay) is more diagnostically useful than the immunofluorescence pattern (c-ANCA vs p-ANCA). Current guidelines favor antigen-specific assays.
Next best step: In suspected AAV, order both PR3-ANCA and MPO-ANCA simultaneously alongside urinalysis with microscopy and serum creatinine.
Imaging:
Tissue biopsy — gold standard for diagnosis:
Board pearl: A kidney biopsy cannot distinguish GPA from MPA — both show pauci-immune crescentic GN. The distinction relies on extra-renal features (upper airway involvement, granulomas) and ANCA type.
Induction (severe/organ-threatening disease):
— Rituximab preferred for: relapsing disease, PR3-ANCA positivity, fertility concerns, younger patients
— Cyclophosphamide preferred when: rituximab is unavailable, or severe alveolar hemorrhage/refractory disease
Next best step: Organ-threatening AAV → start pulse-dose IV steroids immediately → add rituximab or cyclophosphamide within 1–2 days.
Board pearl: Rituximab has become the favored induction agent for most AAV scenarios, especially relapsing GPA.
Once remission is achieved (typically 3–6 months), transition to maintenance:
Duration of maintenance:
Glucocorticoid taper:
Key distinction: Maintenance agent is chosen based on induction agent, ANCA type, relapse history, and organ involvement — not a one-size-fits-all approach.
EGPA treatment differs from GPA/MPA because of its eosinophil-driven pathophysiology:
Non-severe EGPA (no cardiac, renal, GI, or CNS involvement):
Severe EGPA (cardiac, renal, or GI involvement):
Cardiac-specific management:
Board pearl: Mepolizumab is the targeted biologic approved for EGPA — know this for Step 2. It targets IL-5, reducing eosinophil activation.
Key distinction: ANCA-positive EGPA behaves more like classic vasculitis (GN, neuropathy); ANCA-negative EGPA has more cardiac/eosinophilic organ damage.
AAV in pregnancy:
Medication safety:
Monitoring:
Next best step: Woman of childbearing age with AAV → switch to azathioprine maintenance and ensure ≥3-month washout of MTX/MMF before conception.
Elderly patients:
Renal impairment:
Board pearl: Infection is the #1 cause of death in the first year after AAV diagnosis — driven by immunosuppression. Prophylaxis and judicious dosing are critical.
Disease-related complications:
Treatment-related complications:
When to escalate:
Next best step: Rising Cr + active sediment in a known AAV patient on maintenance → suspect relapse → recheck ANCA, urinalysis, consider re-biopsy → re-induce.
Diffuse alveolar hemorrhage (DAH):
Rapidly progressive glomerulonephritis:
Orbital inflammation (GPA):
Board pearl: In DAH, hemoptysis may be absent — a dropping hemoglobin with new bilateral ground-glass opacities should trigger immediate bronchoscopy. Do NOT wait for hemoptysis to act.
Next best step: Suspected pulmonary-renal syndrome → do not delay treatment for ANCA results — start pulse steroids immediately.
Pulmonary-renal syndrome = DAH + GN; differential includes:
— Linear IgG deposits on IF (vs pauci-immune in AAV)
— Anti-GBM antibodies positive
— Young male smoker, rapid course
— Can coexist with AAV ("double-positive") in ~30% of anti-GBM cases
— "Full-house" IF pattern, ↓ complement (C3, C4), ↑ anti-dsDNA
— Other lupus features: malar rash, serositis, cytopenias
— IgA deposits on biopsy; palpable purpura, arthralgias, abdominal pain
— Children > adults
— ↓ complement, ↑ RF, HCV association
— Skin purpura, arthralgias, GN
Key distinction: Normal complement + pauci-immune GN + positive ANCA = AAV. Low complement suggests lupus or cryoglobulinemic vasculitis. Linear IF = anti-GBM.
GPA vs Sarcoidosis:
GPA vs Relapsing polychondritis:
GPA vs Cocaine-induced midline destructive lesion:
Board pearl: Cocaine-induced midline destruction mimics GPA. The ANCA is typically directed against human neutrophil elastase (HNE) — NOT PR3 or MPO. Always check antigen specificity.
Infection prophylaxis (critical during immunosuppression):
— Also has the bonus of reducing GPA relapse in some studies
— Alternative: dapsone or atovaquone
Vaccinations:
Bone health:
Cyclophosphamide-specific:
Disease activity monitoring:
Organ-specific surveillance:
Immunosuppression monitoring:
Board pearl: A rising ANCA titer alone — without clinical evidence of disease activity — is NOT an indication to change therapy.
Board pearl: Always document a fertility preservation discussion before initiating cyclophosphamide — this is both a clinical best practice and a medicolegal standard.
